scholarly journals Effect of amphetamine place conditioning on excitatory synaptic events in the basolateral amygdala ex vivo

Neuroscience ◽  
2012 ◽  
Vol 206 ◽  
pp. 7-16 ◽  
Author(s):  
A. Hetzel ◽  
G.E. Meredith ◽  
D.J. Rademacher ◽  
J.A. Rosenkranz
Keyword(s):  
Basolateral Amygdala ◽  
Ex Vivo ◽  
Place Conditioning

scholarly journals Separable Dorsal Raphe Dopamine Projections Mediate Sociability and Valence

2021 ◽  
Author(s):  
Kay Tye ◽  
Gillian Matthews ◽  
Mackenzie Lemieux ◽  
Elizabeth Brewer ◽  
Raymundo Miranda ◽  
...  
Keyword(s):  
Basolateral Amygdala ◽  
Ex Vivo ◽  
Affective State ◽  
Well Being ◽  
Dorsal Raphe ◽  
Receptor Expression ◽  
Dopamine Neurons ◽  
Bed Nucleus ◽  
Distributed Target ◽  
Dorsal Raphé

Abstract Affiliative social connections facilitate well-being and survival in numerous species. Engaging in social interactions requires positive and negative motivational drive, elicited through coordinated activity across neural circuits. However, the identity, interconnectivity, and functional encoding of social information within these circuits remains poorly understood. Here, we focused on downstream projections of dorsal raphe nucleus (DRN) dopamine neurons (DRNDAT), which we previously implicated in ‘negative drive’-induced social motivation. We show that three prominent DRNDAT projections – to the bed nucleus of the stria terminalis (BNST), central amygdala (CeA), and posterior basolateral amygdala (BLP) – play separable roles in behavior, despite substantial collateralization. Photoactivation of the DRNDAT-CeA projection promoted social behavior and photoactivation of the DRNDAT-BNST projection promoted exploratory behavior, while the DRNDAT-BLP projection supported place avoidance, suggesting a negative affective state. Downstream regions showed diverse, region-specific, receptor expression, poising DRNDAT neurons to act through dopamine, neuropeptide, and glutamate transmission. Furthermore, we show ex vivo that the effect of DRNDAT photostimulation on downstream neuron excitability was predicted by baseline cell properties, suggesting cell-type-specific modulation. Collectively, these data indicate that DRNDAT neurons may bias behavior via precise modulation of cellular activity in broadly-distributed target structures.

scholarly journals Disinhibition-assisted LTP in the prefrontal-amygdala pathway via suppression of somatostatin-expressing interneurons

2019 ◽  
Author(s):  
Wataru Ito ◽  
Brendon Fusco ◽  
Alexei Morozov
Keyword(s):  
Basolateral Amygdala ◽  
Ex Vivo ◽  
Low Frequency ◽  
Long Term Potentiation ◽  
Synaptic Strength ◽  
Neuronal Firing ◽  
High Frequency Stimulation ◽  
Term Potentiation ◽  
Frequency Stimulation

AbstractNatural brain adaptations often involve changes in synaptic strength. The artificial manipulations can help investigate the role of synaptic strength in a specific brain circuit not only in various physiological phenomena like correlated neuronal firing and oscillations but also in behaviors. High and low-frequency stimulation at presynaptic sites has been used widely to induce long-term potentiation (LTP) and depression (LTD), respectively. This approach is effective in many brain areas, but not in the basolateral amygdala (BLA), because the robust local GABAergic tone inside the BLA restricts synaptic plasticity. Here, we identified the subclass of GABAergic neurons that gate LTP in the BLA afferents from the dorsomedial prefrontal cortex (dmPFC). Chemogenetic suppression of somatostatin-positive interneurons (Sst-INs) enabled the ex vivo LTP by high-frequency stimulation of the afferent, but the suppression of parvalbumin-positive interneurons (PV-INs) did not. Moreover, optogenetic suppression of Sst-INs with Arch also enabled LTP of the dmPFC-BLA synapses both ex vivo and in vivo. These findings reveal that Sst-INs but not PV-INs gate LTP in the dmPFC-BLA pathway and provide a method for artificial synaptic facilitation in BLA.

scholarly journals Linking emotional valence and anxiety in a mouse insula-amygdala circuit

2021 ◽  
Author(s):  
Céline Nicolas ◽  
Anes Ju ◽  
Yifan Wu ◽  
Hazim Eldirdiri ◽  
Sebastien Delcasso ◽  
...  
Keyword(s):  
Basolateral Amygdala ◽  
Ex Vivo ◽  
Insular Cortex ◽  
Emotional Valence ◽  
Projection Neurons ◽  
Negative Valence ◽  
Glutamatergic Neurons ◽  
Related Information ◽  
Starting Point ◽  
Positive And Negative Valence

Abstract The response of the insular cortex (IC) and amygdala to stimuli of positive and negative valence were found to be altered in patients with anxiety disorders. However, the coding properties of neurons controlling anxiety and valence remain unknown. Combining photometry recordings and chemogenetics in mice, we uncover the anxiogenic control of projection neurons in the anterior IC (aIC), independently of their projection target. Using viral tracing and ex vivo electrophysiology, we characterize the monosynaptic aIC to the basolateral amygdala (BLA) connection, and employed projection-specific optogenetics, to reveal anxiogenic properties of aIC-BLA neurons in anxiety-related behaviors. Finally, using photometry recordings, we identified that aIC-BLA neurons are active in anxiogenic spaces, and in response to aversive stimuli. Together, these findings show that negative valence, as well as anxiety-related information and behaviors, are encoded by aICBLA glutamatergic neurons, providing a starting point to understand how alterations of this pathway contribute to psychiatric disorders.

scholarly journals Rostral and caudal BLA engage distinct circuits in the prelimbic and infralimbic PFC

2021 ◽  
Author(s):  
Kasra Manoocheri ◽  
Adam G Carter
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Basolateral Amygdala ◽  
Pyramidal Tract ◽  
Ex Vivo ◽  
Layer 2 ◽  
Deep Layers ◽  
Local Circuits ◽  
Whole Cell Recordings

Connections from the basolateral amygdala (BLA) to medial prefrontal cortex (PFC) regulate memory and emotion and become disrupted in neuropsychiatric disorders. We hypothesized that the diverse roles attributed to interactions between the BLA and PFC reflect multiple circuits nested within a wider network. To assess these circuits, we first used anatomy to show that the rostral BLA (rBLA) and caudal BLA (cBLA) differentially project to prelimbic (PL) and infralimbic (IL) subregions of the PFC, respectively. We then combined in vivo silicon probe recordings and optogenetics to show that rBLA primarily engages PL, whereas cBLA mainly influences IL. Using ex vivo whole-cell recordings and optogenetics, we then assessed which neuronal subtypes are targeted, showing that rBLA preferentially drives layer 2 (L2) cortico-amygdalar (CA) neurons in PL, whereas cBLA drives layer 5 (L5) pyramidal tract (PT) cells in IL. Lastly, we used soma-tagged optogenetics to explore the local circuits linking superficial and deep layers of PL, showing how rBLA can also impact L5 PT cells. Together, our findings delineate how subregions of the BLA target distinct networks within the PFC to have different influence on prefrontal output.

scholarly journals A novel mitragynine analog with low efficacy mu-opioid receptor agonism displays antinociception with attenuated adverse effects

2021 ◽  
Author(s):  
Soumen Chakraborty ◽  
Jeffrey F Diberto ◽  
Abdelfattah Faouzi ◽  
Sarah M bernhard ◽  
Anna M Gutridge ◽  
...  
Keyword(s):  
G Protein ◽  
Opioid Receptor ◽  
Ex Vivo ◽  
Mu Opioid Receptor ◽  
Place Conditioning ◽  
Mu Opioid ◽  
Synaptic Physiology ◽  
Protein Assays ◽  
Efficacy Profile

Dried kratom leaves are anecdotally used for the treatment of pain, opioid dependence, and alcohol use disorder. We have previously shown that kratom and its natural products (mitragynine) and semi-synthetic analogs (7-hydroxy mitragynine (7OH) and mitragynine pseudoindoxyl) are mu opioid receptor (MOR) agonists that show minimal beta-arrestin2 recruitment. To further investigate the structure activity relationships of G-protein potency, efficacy, and beta-arrestin2 recruitment, we diversified the mitragynine/7OH templates at the C9, -10 and -12 positions of the aromatic ring of the indole moiety. Three lead C9 analogs, synthesized by swapping the 9-methoxy group with varied substituents, namely phenyl (SC11), methyl (SC12), 3-furanyl (SC13), were further characterized using a panel of in vitro and ex vivo electrophysiology assays. All three compounds were partial agonists with lower efficacy than both DAMGO and morphine in heterologous G-protein assays and synaptic physiology. SC11-13 also showed lower recruitment of both β-arrestin subtypes compared to DAMGO, and in assays with limited MOR receptor reserve, the G-protein efficacy of SC11, SC12 and SC13 was comparable to buprenorphine. In mouse models, at equianalgesic doses SC13 showed MOR-dependent analgesia with potency similar to morphine without respiratory depression, hyperlocomotion, constipation, or place conditioning. Taken together, these results suggest that MOR agonists with a G-protein efficacy profile similar to buprenorphine can be developed into opioids that are effective analgesics with greatly reduced liabilities.

scholarly journals Cyclooxygenase-2 inhibition reduces stress-induced affective pathology

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Joyonna Carrie Gamble-George ◽  
Rita Baldi ◽  
Lindsay Halladay ◽  
Adrina Kocharian ◽  
Nolan Hartley ◽  
...  
Keyword(s):  
Anxiety Disorders ◽  
Basolateral Amygdala ◽  
Cannabinoid Receptor ◽  
Ex Vivo ◽  
Receptor Activation ◽  
Cyclooxygenase 2 ◽  
Novel Treatment ◽  
Cox 2 ◽  
Cox 2 Inhibitors

Mood and anxiety disorders are the most prevalent psychiatric conditions and are exacerbated by stress. Recent studies have suggested cyclooxygenase-2 (COX-2) inhibition could represent a novel treatment approach or augmentation strategy for affective disorders including anxiety disorders and major depression. We show that traditional COX-2 inhibitors and a newly developed substrate-selective COX-2 inhibitor (SSCI) reduce a variety of stress-induced behavioral pathologies in mice. We found that these behavioral effects were associated with a dampening of neuronal excitability in the basolateral amygdala (BLA) ex vivo and in vivo, and were mediated by small-conductance calcium-activated potassium (SK) channel and CB1 cannabinoid receptor activation. Taken together, these data provide further support for the potential utility of SSCIs, as well as traditional COX-2 inhibitors, as novel treatment approaches for stress-related psychiatric disorders.

scholarly journals Ethanol-induced conditioned place preference and aversion differentially alter plasticity in the bed nucleus of stria terminalis

2019 ◽  
Author(s):  
Dipanwita Pati ◽  
Melanie M. Pina ◽  
Thomas L. Kash
Keyword(s):  
Conditioned Place Preference ◽  
Drugs Of Abuse ◽  
Ex Vivo ◽  
Glutamate Release ◽  
Place Preference ◽  
Place Conditioning ◽  
Stria Terminalis ◽  
Drug Seeking ◽  
Bed Nucleus ◽  
Seeking Behavior

AbstractContextual cues associated with drugs of abuse, such as ethanol, can trigger craving and drug seeking behavior. Pavlovian procedures, such as place conditioning, have been widely used to study the rewarding/aversive properties of drugs and the association between environmental cues and drug seeking. Previous research has shown that ethanol as an unconditioned stimulus can induce a strong conditioned place preference (CPP) or aversion (CPA) in rodents. However, the neural mechanisms underlying ethanol induced reward and aversion have not been thoroughly investigated. The bed nucleus of the stria terminalis (BNST), an integral part of the extended amygdala, is engaged by both rewarding and aversive stimuli and plays a role in ethanol seeking behavior. Here, we used ex-vivo slice physiology to probe learning-induced synaptic plasticity in the BNST following ethanol-induced CPP and CPA. Male DBA/2J mice (2-3 months old) were conditioned using previously reported ethanol-induced CPP/CPA procedures. Ethanol-induced CPP was associated with increased neuronal excitability in the ventral BNST (vBNST). Conversely, ethanol-induced CPA resulted in a significant decrease in spontaneous glutamatergic transmission without alterations in GABAergic signaling. Ethanol-CPA also led to significant increase in paired pulse ratio at excitatory synapses, suggestive of a decrease in presynaptic glutamate release. Collectively, these data demonstrate that the vBNST is involved in the modulation of contextual learning associated with both the rewarding and the aversive properties of ethanol in mice.

scholarly journals Amygdala-cortical control of striatal plasticity drives the acquisition of goal-directed action

2020 ◽  
Author(s):  
Simon D. Fisher ◽  
Lachlan A. Ferguson ◽  
Jesus Bertran-Gonzalez ◽  
Bernard W. Balleine
Keyword(s):  
Basolateral Amygdala ◽  
Ex Vivo ◽  
Projection Neurons ◽  
Cortical Control ◽  
Indirect Pathway ◽  
Optogenetic Stimulation ◽  
Directed Action ◽  
Directed Learning ◽  
Corticostriatal Plasticity ◽  
Stimulation Of

SummaryThe acquisition of goal-directed action requires the encoding of specific action-outcome associations involving plasticity in the posterior dorsomedial striatum (pDMS). We first investigated the relative involvement of the major inputs to the pDMS argued to be involved in this learning-related plasticity, from prelimbic prefrontal cortex (PL) and from the basolateral amygdala (BLA). Using ex vivo optogenetic stimulation of PL or BLA terminals in pDMS, we found that goal-directed learning potentiated the PL input to direct pathway spiny projection neurons (dSPNs) bilaterally but not to indirect pathway neurons (iSPNs). In contrast, learning-related plasticity was not observed in the direct BLA-pDMS pathway. Using toxicogenetics, we ablated BLA projections to either pDMS or PL and found that only the latter was necessary for goal-directed learning. Importantly, transient inactivation of the BLA during goal-directed learning prevented the PL-pDMS potentiation of dSPNs, establishing that the BLA input to the PL is necessary for the corticostriatal plasticity underlying goal-directed learning.

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